2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid, and meso-2,3-dimercaptosuccinic acid inhibit delta-aminolevulinate dehydratase from human erythrocytes in vitro.

The effects of dithiol chelating agents meso-2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane-1-sulfonic acid (DMPS), and 2,3-dimercaptopropanol (BAL) on delta-aminolevulinate dehydratase (delta-ALA-D) from human erythrocytes were evaluated. Furthermore, possible protective effects of zinc chloride (ZnCl(2)), dithiothreitol (DTT), and cysteine were studied. delta-ALA-D activity from human erythrocytes was inhibited by dithiol chelating agents in a concentration-dependent manner. Cysteine, at all concentrations tested, did not protect the inhibitory effect of 1 and 4 mM DMPS and DMSA, but protected 1 mM BAL inhibition. Dithiotreitol was able to protect the inhibition caused by 1 mM BAL (28%), DMPS (56%), and DMSA (40%) in a concentration-dependent manner. Zinc chloride protected and restored 1 mM BAL inhibitory effect on delta-ALA-D. Zinc chloride at 500 microM and 1 mM, respectively, protected inhibitory effects of DMPS and DMSA (1 and 4 mM), but did not reverse its effects. The preincubation of dithiol chelating agents with enzyme demonstrated that DMSA was the most potent delta-ALA-D inhibitor of human erythrocytes. These data are in agreement with delta-ALA-D activity from purified enzyme. ZnCl(2) (1 microM) added, in the reaction mixture, increased enzyme activity and DTT (100 microM) totally restored the enzyme activity for all chelating agents tested.